Regulation of glial Na+/K+-ATPase by serotonin: Identification of participating receptors

The purpose of the present study was the characterization of the receptors participating in the regulatory mechanism of glial Na+/K+-ATPase by seroton in (5-HT) in rat brain. The activity of the Na+ pump was measured in four b rain regions after incubation with various concentrations of serotoninergic agonists or antagonists. A concentration-dependent increase in enzyme acti vity was observed with the 5-HT1A agonist R (+)-2-dipropylamino-8-hydroxy-1 ,2,3, 4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) in homogenates or in glial membrane enriched fractions from cerebral cortex and in hippocampus. Spiperone, a 5-HT1A antagonist, completely inhibited the response to 8-OH- DPAT but had no effect on Na+/K+-ATPase activity in cerebellum where LSD, a 5-HT6 agonist, elicited a dose-dependent response similar to that of 5-HT. In brainstem, a lack of reponse to 5-HT and other agonists was confirmed. Altogether, these results show that serotonin modulates glial Na+/K+-ATPase activity in the brain, apparently not through only one type of 5-HT recept or. It seems that the receptor system involved is different according to th e brain region. In cerebral cortex, the response seems to be mediated by 5- HT1A as well as in hippocampus but not in cerebellum where 5-HT6 appears as the receptor system involved.